We have recently described a class-switched (IgM to IgG1) human-mouse chimeric antibody. In the present study, a human-mouse chimeric antibody specific for human adenocarcinoma-assocated atigen YH206 antigen was costrcted by fusing murine varible region genes (Vκ and VH) to human cnstant region genes (γ1,κ) The murine variable domain genes were isolated from a funconal murine hybridoma cell line, YH206, which secreted IgM monoclonal antibody specific for YH206 antgen. The fusion gens of heavy and light chins were introduced into the immunoglobulin non-prodcing mouse myeloma cell line X63-Ag8.653 by electroporation. We obtained transformants which secreted class-switched human-mouse chimeric antibodies specific for YH206 antigen. A dot immunobinding assay demonstrated that the class-switched chimeric antibody retained the ability to bind to the YH206 antigen.
Metabolomic studies conducted for evaluating cancer pathogenesis and progression by monitoring the amino acids metabolic balance hold great promise for assessing current and future anticancer treatments. We performed a comprehensive quantification of 21 amino acids concentrations in cultured human colorectal adenocarcinoma cells treated with the anticancer drugs 5-fluorouracil, irinotecan, and cisplatin. A precolumn fluorescence derivatization-HPLC method involving 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was used. Amino acid concentration data were analyzed by principal-component analysis and partial least-squares multivariate statistical methods to represent samples on two-dimensional graphs. The hierarchical cluster analysis and linear discriminant analysis were used to classify the samples on the score plots. Unlike the cluster analysis approach, the linear discrimination analysis classification successfully distinguished anticancer drug-treated samples from the untreated controls. Moreover, three candidate amino acids (serine, aspartic acid, and methionine) were identified from the loading plots as potential biomarkers. Our proposed method might be able to evaluate the effectiveness of anticancer therapy even in small laboratories or medical institutions.
RCAS1 is a receptor-binding cancer antigen which is expressed on human uterine cervical adenocarcinoma cell line (SiSo). Finding a correlation between the expression of this gene and the overall survival of patients with 14 different types of cancer points to the clinical significance of this gene. Moreover, the expression RCAS1 correlates with other clinicopathological parameters including the histological type of cancer, its differentiation, tumor size, clinical stage, the depth of invasion, lymphovascular space involvement, lymph node metastasis, and positive peritoneal cytological results. RCAS1 can induce apoptosis in peripheral lymphocytes in vitro as well as in an increased number of apoptotic tumor-infiltrating lymphocytes. RCAS1 is also believed to contribute to the escape of tumor cells from immune surveillance. RCAS1 is secreted via ectodomain shedding, and its expression is related to changes in the characteristics of the extracellular matrix and to a reduced number of vimentin-positive tumor stromal cells, findings that suggest that RCAS1 may induce connective tissue remodeling. The concentration of RCAS1 in serum or pleural effusions has been found to be significantly higher in patients with several different types of cancer as compared to normal controls. Together, the available data shows that RCAS1 may have value as a biomarker for monitoring therapeutic efficacy. Further exploration of the biological function of RCAS1 should help in the development of new therapeutic strategies against human malignancies.
Abstract Collagen type XVII (COL17) is expressed in various tissues and its aberrant expression is associated with tumour progression. In this study, we investigated the regulation of COL17 expression in oral squamous cell carcinoma (OSCC) using the cell lines NA, SAS, Ca9-22, and Sa3. COL17 was induced upon p53 activation by cisplatin in SAS; however, this effect was more limited in NA and hardly in Ca9-22 and Sa3, with mutated p53. Moreover, COL17 was found to be regulated by miR203a-3p in all cell lines. Our data suggest that COL17 expression in OSCC cell lines is regulated by p53 and miR203a-3p.
Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore, it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently, extracellular vesicles—particularly exosomes—have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer‐dependent manner. Previous studies have shown inconsistent results regarding miR‐200c‐3p expression levels in OSCC cell lines, tissues, or serum—likely because of the heterogeneous characters of the specimen materials. For this reason, single‐cell clone analyses are necessary to effectively assess the role of exosome‐derived miRNAs on cells within the tumor microenvironment. The present study utilized integrated microarray profiling to compare exosome‐derived miRNA and exosome‐treated cell‐derived mRNA expression. Data were acquired from noninvasive SQUU‐A and highly invasive SQUU‐B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa‐miR‐200c‐3p was a key pro‐invasion factor among six miRNA candidates. Consistently, silencing of the miR‐200c‐3p targets, CHD9 and WRN , significantly accelerated the invasive potential of SQUU‐A cells. Thus, our data indicate that miR‐200c‐3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non‐invasive counterparts.
